The search for novel antibiotics is of direct human health relevance because of the increase in microbial resistance to conventional antibiotics and a deficit in new drugs (1, 2). Coral reefs are the most biodiverse of marine ecosystems and a source of novel antibiotics, but they are threatened due to disease, climate change, and pollution (3). Since marine bacteria can produce compounds that are chemically distinct from their terrestrial counterparts (4), it is imperative to catalog and characterize the unknown microbial diversity in corals and their potential antibiotics. The main objectives of this work are to characterize antibiotics from marine bacteria associated with a coral, and to study the functional role of the antibiotic insult on a pathogen's physiology. The first aim will ascertain the antimicrobial activity of bacteria isolated from Pseudopterogorgia americana surface mucopolysaccharide layer (SML), which is a carbon-rich habitat for an abundant and diverse microbial community (5). The SML selects for symbiotic bacteria with antimicrobial activity that may protect the coral host by detemng pathogenic microorganisms (6, 7). We will use an agar- overlay antimicrobial assay to determine the antimicrobial production of P. americana's SML-associated bacteria against seven microorganisms relevant to human and corals. The second aim specifically targets NIAID/NIH's mission for drug discovery by identifying and characterizing antimicrobial compounds from a broad-spectrum antimicrobial coral isolate, and surveying its genetic bioactive potential with molecular techniques. Antibiotic compound(s) will be purified and structurally characterized using chromatographic (e.g., HPLC), mass spectrometric (e.g., LC-MS), and spectroscopic (NMR) techniques. Molecular techniques will be performed to determine presence of genes known to produce bioactive compounds. The third aim will analyze a possible mechanism of antibiotic action against a coral pathogen through metabolic profile characterization of its co-culture with the antimicrobial coral isolate. We will utilize metabolomics to analyze the intracellular changes of a Vibrio pathogen when in presence of an antimicrobial coral isolate, focusing on metabolic changes (e.g., DNA, RNA, protein synthesis) using NMR analysis. Relevance- The World Health Report categorized microbial antibiotic resistance as a major threat to public health, which is augmented due to the diminished developmental research for new antibiotic drugs (8). This project seeks to meet this demand by characterizing potentially novel antibiotic(s) and their function on a microbial pathogen's physiology.